The proposed research aims to systematically investigate the associations of adolescent anxiety, depression, and their comorbidity with hypothalamic-pituitary-adrenal (HPA) function, considering potential differences by context, gender, early life experiences, and individual biobehavioral factors. Research design and methods: This project will focus especially on HPA reactivity (indexed by salivary cortisol) to an acute psychosocial stressor. Using a newly-developed exportable adolescent version of the Trier Social Stress Test (TSST), this study will distinguish reactivity during anticipatory, task, and recovery periods and in unfamiliar vs. familiar contexts. During Grade 12 (approximate age 18 years), adolescents (n=96) will be recruited from the Wisconsin Study of Families and Work, a longitudinal community study of child/adolescent development (N=417). Based on levels of anxiety and/or depression symptoms averaged over Grades 9, 10 and 11, half (n=48) will be selected for high levels of anxiety and/or depression symptoms;the other half (n=48) will be randomly selected from the lower half of both distributions. Each group of 48 will be randomly assigned to assessments conducted either in the laboratory (unfamiliar context;n=24) or home (familiar context;n=24), balanced for gender. HPA basal activity also will be assessed over 3 days to characterize diurnal patterns. Interviews and questionnaires with adolescents and their mothers will ascertain recent life stressors, adolescent cognitive attributions/biases, and adolescent mental health symptoms and impairments. Full diagnostic psychiatric evaluations (K-SADS) will be obtained. Specific aims: (1) to investigate (a) the associations of HPA diurnal patterns (overall levels and daily slope of cortisol) and reactivity to an acute psychosocial stressor (TSST), differentiating anticipatory, task, and recovery components, and (b) differences by context (unfamiliar laboratory vs familiar home) and gender;(2) to investigate (a) the associations of HPA activity (diurnal and reactive, as defined in Aim 1) with adolescent anxiety and/or depression, and (b) differences by context and gender;and (3) to explore (a) differences in the associations found in Aims 1 and 2 by adolescents'earlier histories of stress exposure, HPA diurnal patterns, and temperamental inhibition, and (b) differences by context and gender. This application is consistent with the goals of PAR-06-473, "Translational Research on the Relationship of Anxiety and Depression". It is interdisciplinary, addressing questions integrating biological, neuroendocrine stress-response systems with contextual and individual factors;it is exploratory, including a newly-developed adolescent version of the TSST that is exportable to field settings;and, it is translational, integrating basic science research with the study of adolescent mental health. PUBLIC HEALTH RELEVANCE: By looking at hypothalamic-pituitary-adrenal (HPA) function, the proposed project will provide insight into the underlying pathophysiology of comorbid anxiety and depression in adolescence, which has relevance for the development of effective pharmacological and other treatments. Further, by taking advantage of the longitudinal data available in the Wisconsin Study of Families and Work, the proposed project can look at the development of comorbid anxiety/depression and what early experiences and child characteristics are risk factors for these later processes, work that is important for the development of early prevention efforts.